Immunologic Incompetence of the Neoplastic Lymphocyte in Chronic Lymphocytic Leukemia

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Abstract
The comparative immune response of the leukemic and the normal lymphocyte was studied by using a visible manifestation of an antigen-antibody reaction on the surface of those cells as an indicator of their ability to produce antibody. The experimental method consisted of serially immunizing healthy individuals and patients with chronic lymphocytic leukemia with a polyvalent Salmonella antigen and periodically harvesting their peripheral blood lymphocytes by differential centrifugation. After thorough washing, the cells were incubated with the bacterialimmunogen and wet coverslip preparations were examined under dark-field and phase microscopy. Adherence of bacteria to the surface of the lymphocyte was taken as evidence of an antigen-antibody combination. The physicochemical nature of the antibody was characterized by exposing the lymphocytes to mercaptoethanol (ME). Under the conditions described, bacteria aggregated firmly on the surface of normal lymphocytes and could be prevented from assuming this position or detached by ME. Bacteria never were seen on the surface of red cells, indicating that humoral salmonella antibody was not merely adsorbed on the normal lymphocyte but originated in this cell. In contrast, leukemic lymphocytes were singularly free of bacterial adherence. These observations suggest that normal peripheral blood lymphocytes synthesize 19S, ME-sensitive antibody against a specific bacterial antigen. More important, however, was the failure of neoplastic lymphocytes to react in an analogous manner. This immunologic indolence may reflect a basic biologic difference between normal and leukemic lymphocytes. It may also explain the susceptibility of patients with chronic lymphocytic leukemia to gram-negative sepsis, infections which require the protective participation of the 19S immuno-globulins.